U.S. Pat. No. 4,748,023 discloses a process for the preparation of sustained release solid pharmaceutical compositions comprising active ingredient crystals coated with a single layer of ethylcellulose, while U.S. Pat. Nos. 4,259,315, 4,572,833, and 4,832,955 disclose the preparation of sustained release solid pharmaceutical compositions comprising a potassium chloride core coated with a water insoluble ethylcellulose layer containing a hydrophobic material, a high HLB surfactant, and an amphiphile, respectively. U.S. Pat. No. 4,863,743 to Hsiao and Chou of Key Pharmaceuticals teaches a controlled release pharmaceutical dosage form comprising a dissolution rate controlling membrane on potassium chloride crystals. The dissolution rate controlling membrane includes a high viscosity water insoluble ethylcellulose in combination with a water-soluble hydroxypropylcellulose or polyethylene glycol applied from a fluid bed coater. The coated granules are blended with highly compressible microcrystalline cellulose, a disintegrant, and a lubricant (for example, magnesium stearate) and compressed into 10 or 20 mEq tablets. The resulting tablets are of acceptable hardness and friability (for example, 20 mEq tablets weighing about 2 g, exhibit a hardness of not less than 14 kP and a friability of not more than 0.3). The controlled release tablets thus produced rapidly disperse into granules upon exposure to water or body fluids, and these granules provide an extended release of potassium, i.e., releasing not more than 40% in one hour, from about 60% to about 75% in 4 hours, and not less than 80% in 8 hours when tested by USP Apparatus 2 (Paddles @ 50 rpm) in purified water. Thus, these tablets can be transported in normal storage drums for commercial distribution to pharmacies and hospitals.
Powell, in U.S. Pat. Nos. 5,422,122 and 5,651,984, teaches the preparation of controlled release 10 and 20 mEq potassium chloride tablets by first forming KCl microcapsules by coacervation in a cyclohexane solution of high viscosity water insoluble ethylcellulose and over-coating the microcapsules with at least one hydrophilic polymer to impart compressibility properties to otherwise poorly compressible microcapsules. The coated microcapsules are blended with highly compressible microcrystalline cellulose and a disintegrant to be compressed into tablets. Tablets produced from microcapsules coated with hydroxypropylcellulose exhibit the desired drug release characteristics (high hardness and low friability, providing controlled release profiles). However, compression of a mixture wherein the microcapsules are coated with hydroxypropyl methylcellulose (HPMC) or polyvinylpyrrolidone (PVP) and blended with microcrystalline cellulose, crosslinked PVP (disintegrant) and magnesium chloride failed to produce tablets of acceptable hardness and friability. Moreover, controlled release tablets comprising potassium chloride microcapsules coated with a plasticized hydroxypropyl methylcellulose or polyvinylpyrrolidone, highly compressible microcrystalline cellulose, and a disintegrant exhibited drug release profiles faster than the reference tablets (Hsiao tablets or K-Dur 20). By contrast, the tablets containing none of the widely used disintegrants exhibited in vitro drug release profiles similar to that of the Hsiao tablets and hence, proved to be bioequivalent to the Hsiao tablets. However, these tablets failed to meet the ‘industrial use’ test criterion because they failed to rapidly disperse into granules on contact with water. It is thus apparent that the described process or method of manufacturing of controlled release of potassium chloride tablets fails to meet all of the industrial applicability criteria, namely, product quality, suitability for packaging in HDPE bottles and blisters for storage, transportation, commercial distribution, and use.